Intra-cavitary dosimetry for IMRT head and neck treatment using thermoluminescent dosimeters in a naso-oesophageal tube.

Complex intensity-modulated radiation therapy (IMRT) treatment plans require rigorous quality assurance tests. The aim of this study was to independently verify the delivered dose inside the patient in the region of the treatment site. A flexible naso-gastric tube containing thermoluminescent dosimeters (TLDs) was inserted into the oesophagus via the sinus cavity before the patient's first treatment. Lead markers were also inserted into the tube in order that the TLD positions could be accurately determined from the lateral and anterior-posterior electronic portal images taken prior to treatment. The measured dose was corrected for both daily linac output variations and the estimated dose received from the portal images. The predicted dose for each TLD was determined from the treatment planning system and compared to the measured TLD doses. The results comprise 431 TLD measurements on 43 patients. The mean measured-to-predicted dose ratio was 0.988 +/- 0.011 (95% confidence interval) for measured doses above 0.2 Gy. There was a variation in this ratio when the measurements were separated into low dose (0.2-1.0 Gy), medium dose (1.0-1.8 Gy) and high dose (>1.8 Gy) measurements. The TLD-loaded, naso-oesophageal tube for in vivo dose verification is straightforward to implement, and well tolerated by patients. It provides independent reassurance of the delivered dose for head and neck IMRT.

The early growth response gene EGR-1 behaves as a suppressor gene that is down-regulated independent of ARF/Mdm2 but not p53 alterations in fresh human gliomas.

PURPOSE: EGR-1 is an immediate early gene with diverse functions that include the suppression of growth. EGR-1 is down-regulated many cancer cell types, suggesting a tumor suppressor role, and may critically involve the p53 pathway. The aim of this work was to measure the expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in fresh human gliomas. EXPERIMENTAL DESIGN: Thirty-one human gliomas with different grades of malignancy were investigated for Egr-1 mRNA and the protein expression, frequency, and spectrum of p53 gene mutations, mdm2 gene amplification, and p16/INK4a/ARF allele loss. RESULTS: The amplification of Mdm2 and the deletion of the p16/INK4a gene was found in 3 and 5 cases, respectively, whereas mutations of p53, including two novel mutations, were observed in 10 other cases. The three types of changes occurred strictly mutually exclusively, emphasizing that these genes operate in a common pathway critical to glioma progression. EGR-1 mRNA was significantly down-regulated in astrocytomas (14.7 +/- 5.1%) and in glioblastomas (33.6 +/- 10.0%) versus normal brain. Overall, EGR-1 mRNA was strongly suppressed (average, 15.2 +/- 13.9%) in 27 of 31 cases (87%), independent of changes in p16/INK4a/ARF and Mdm2; whereas 4 of 31 cases with residual EGR-1 expression as well as the highest EGR-1 variance segregated with p53 mutations. Immunohistochemical analyses confirmed the suppression of EGR-1 protein. CONCLUSIONS: These results indicate that EGR-1 is commonly suppressed in gliomas independent of p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors bearing p53 mutations, and these results implicate an EGR-1 growth regulatory mechanism as a target of inactivation during tumor progression.

Unilateral reduction of head pain and facial vasodilatation after gasserian ganglion lesion.

The features of histamine-induced headache and its associated vascular responses were studied in 52 patients with different surgical lesions of the gasserian ganglion and in 12 control subjects. Certain features of headache (eg, intensity, type, and duration) were similar in patients and control subjects. However, the pain was absent on the side of the trigeminal lesion in 26 (50%) of the patients. This unilateral absence of pain was not related to the hypoesthesia that was caused by the operation, and it was associated with a decrease in vascular responses (histamine-induced facial flushing and increase in temperature) on the side operated on. These abnormalities were more prevalent in patients who had undergone thermocoagulation and presented with more severe damage of the trigeminal ganglion than in those who were subjected to trigeminal compression or glycerolization. The trigemino-vascular system seems to control headache of a vascular type and associated craniofacial vasodilatation in human subjects.

Long-term results of the surgical treatment of spinal dermoid and epidermoid tumors.

The clinical findings and the results of surgical treatment in 16 patients with spinal dermoid or epidermoid tumors are reported. In 9 patients the tumor capsule adhered so tightly to the nervous tissue that part of it was left in situ. In a follow-up study ranging from 5 to 30 years with a mean of 14.2 years only 1 patient had a recurrence of the tumor and 10 patients resumed a normal working life.

Epidermoid tumors of the 4th ventricle: report of seven cases.

Epidermoid tumors occur very rarely in the 4th ventricle. We discuss the history, clinical course, and the surgical results for seven patients. One patient had a remittal of symptoms, probably due to the emergence of the tumor from the 4th ventricle into the cisterna magna. Total removal of the capsule was possible only in the youngest patient. At present, four patients (mean follow-up, 6 years) enjoy good general and neurological health.

Intradural extramedullary cavernous angioma: case report.

Cavernous angiomas represent 5 to 12% of spinal vascular malformations and usually are located at the vertebral body level with possible extension into the extradural space. The intradural intramedullary cavernoma occurs in about 3% of cases, whereas extramedullary localization is extremely rare. A new case of an intradural extramedullary cavernous angioma is reported, and the clinical, diagnostic, and therapeutic aspects of this rare malformation are analyzed.

Epidermoid and dermoid cysts. Clinical evaluation and late surgical results.

The authors report on the clinical data, operating technique, postoperative complications, and late results in a series of 31 epidermoid and 21 dermoid cysts of the central nervous system.

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial.

BACKGROUND: Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only. PATIENTS AND METHODS: Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial. In phase I of the study, TMZ (75 mg/m2/day per 7 days/wk for 6 weeks) was orally administered to patients concomitantly with radiotherapy (RT) (2 Gy per fraction once daily, per 5 days/wk for 6 weeks). In phase II of the study, four weeks after completion of RT, a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles. Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry. RESULTS: The one-year survival rate of patients treated with the investigated multimodality treatment was 58% and median survival time was 15.7 months. Concomitant RT plus TMZ (phase I) followed by adjuvant TMZ (phase 2) were well-tolerated; indeed, nonhematological adverse events were rare and mild to moderate in severity; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II. We found that the combination of radio- and chemo-therapy, in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study. CONCLUSION: The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients' quality of life.

Intracerebral schwannoma. Case report.

A case of intraparenchymal schwannoma is presented. A 61-year-old woman, with stigmata of von Recklinghausen's neurofibromatosis (NF-2), presented with a history of weakness of the right lower limb for 2 months. She was investigated by MR which showed a circular mass with a maximum diameter of 5 cm in the right parieto-occipital lobe. The tumor was removed in toto via a left parieto-occipital craniotomy. The patient was discharged two weeks after the operation and remains well now 2 years later. The clinical and neuroradiological findings of reported intraparenchymal schwannomas, including the case reported here, are discussed.

Trigeminal schwannoma with infratemporal extension. Case report.

The case of a 55-year-old woman with a rare trigeminal schwannoma extending into the infratemporal fossa is described. The presentation and treatment of this type of intra and extracranial tumor are discussed.

Solitary cerebral metastasis from melanoma: value of the 'en bloc' resection.

The authors report 19 cases of solitary cerebral metastases from malignant melanoma. In 15 patients, the primary lesion was known at the time the metastasis was diagnosed; deltoid-scapular in 4 cases, thoracic in 5, inguinal in 4 and neck in 2. The primary location was unknown in 4 patients. Presenting symptoms were: epileptic seizures in 9 cases, headache in 8, strength deficit of the limbs in 2. In 3 patients (16%) neurological symptoms were the first clinical sign of the systemic tumor; in 16 cases (84%) there was a long interval between treatment of the primary and appearance of the cerebral metastasis (average 3.8 years; median 3.4 years). All patients were submitted to surgery and radiotherapy (whole-brain in 14 and radiosurgery in 5). In 10 cases the lesion was removed 'en bloc' (no internal touch technique). Average survival was 9 months (median 8 months) and was influenced by 'en bloc' resection and whole-brain irradiation. None of the patients operated by the 'no touch technique' presented a recurrence.

Brain metastases from hepatocellular carcinoma. A case report.

Brain metastasis from hepatocarcinoma are a decidedly rare occurrence in countries where this pathology is most frequent. The authors describe a case of metastases from hepatocellular carcinoma in a patient suffering from post-HBV hepatic cirrhosis with hemorrhagic onset. The "stroke-like" presentation of the cerebral localization of the disease can be explained by both the important vascularization of the tumor and the frequent hemocoagulative alterations caused by the cirrhosis. The importance of diagnostic neuroradiology is briefly addressed, with reference to the fundamental role played by MRI. Surgery of these lesions does not present any particular technical problems as long as they are located in accessible areas and the patient's general and neurological conditions allow it. Postoperative radiotherapy seems to improve the quality and quantity of residual life, although the number of patients described in the literature is too small to draw any definite conclusion. Promising molecular biology studies are under way to evaluate the role of oncosuppresor gene expression in hepatocarcinogenesis and in the way the disease spreads.

Use of spiral computerized tomography angiography in patients with cerebral aneurysm. Our experience.

BACKGROUND: The purpose is to highlight the usefulness of CT angiography (CTA) in the diagnosis and surgical treatment of cerebral aneurysms. METHODS: Thirty-one patients with subarachnoid haemorrhages were subjected to CT angiography and in those cases where this test did not reveal the aneurysm or did not supply sufficient information relating to it, subsequently a digital subtraction angiography was also performed. Each aneurysm-positive CTA was re-processed using the 3-D techniques, with the neuro-radiologist and the neuro-surgeon working in close co-operation. RESULTS: In 27 cases the CTA diagnosed an aneurysm, and in the 4 cases where no vascular malformations were revealed, also the traditional angiography did not show any pathology. In 17 out of 18 cases operated on in order to clip the aneurysm, the CTA supplied all the information needed for the surgery and it was possibile to reconstruct images similar to those of the surgical field. This led to improvement in the programming of the surgical intervention; in 1 case only was it also necessary to perform the DSA before the operation. CONCLUSIONS: CT angiography, because it is non-invasive, easy to perform, diagnostically reliable, and because the 3-D re-constructions offer the chance to create images of the possible operating field, is the first-choice test to be adopted in the treatment of subarachnoid haemorrhages, even though in some cases the use of the traditional angiography is still necessary and should be carried out whenever the CTA does not reveal vascular malformations.

Intracranial meningiomas related to external cranial irradiation.

Three cases are presented of meningiomas following small-dose external cranial irradiation in which several features clearly indicate a causal relationship between radiotherapy and tumour development. In two of them, multiple meningiomas followed X-ray treatment for Tinea capitis. The length of the latent period separates meningiomas following high-dose irradiation, usually administered for intracranial tumours, from those which followed small-dose irradiation. Therefore the oncogenic mechanism seems to act differently in the two groups. This demonstration that multiple meningiomas can occur in patients irradiated for Tinea capitis should enable other similar cases to be recognized.

Dermoid cysts of the posterior cranial fossa in children. Report of nine cases and review of the literature.

Dermoids of the posterior cranial fossa in children are rare. We report the clinical and pathological data on nine children with these lesions. A mean follow-up of 17.3 years after total removal confirms the excellent prognosis irrespective of whether the presenting symptom is meningitis or intracranial hypertension. A brief review of 39 published cases follows.

Intramedullary meningioma: case report and review of the literature.

Intramedullary meningioma is a rarely reported clinical entity. As far as we know, only three cases have been reported to date. We describe a further case at the cervical level and review the few published cases.

Sarcoma metastatic to the brain: a series of 15 cases.

METHODS: We report on 15 patients surgically treated for intraparenchymal brain metastases from sarcoma, including six osteosarcomas, five leiomyosarcomas, two malignant fibrous histiocytomas, and two alveolar soft-part sarcomas (ASPS). RESULT: Median survival after craniotomy was 9.3 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3 months for those with a Karnofsky performance score < 70 (p=0.03). Patients with evidence of only lung metastases at the time of surgery (nine cases) survived 8.6 months, which was similar to the 10.4-month survival for patients with disease limited to the brain (p=0.1). The two patients with alveolar soft-part sarcomas are alive at 15 and 20 months after surgery. CONCLUSION: We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from ASPS may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis; the presence of concurrent lung metastases is not a contraindication to surgery.

Meningiomas of the lateral ventricles. Clinical, neuroradiologic, and surgical considerations in 19 cases.

The clinical and neuroradiologic findings and surgical results in a series of 19 patients with lateral ventricle meningioma, operated on during a 33-year period, are described. This experience is compared with that of previous workers and the following conclusions are drawn: these tumors have no characteristic symptoms; preoperative diagnosis requires both computed tomography scans and carotid and vertebral angiography; the safest surgical approach is through a sagittal or oblique parietooccipital cortical incision to avoid damage to motor, visual, and speech areas of the cortex.

High-dose radiation-induced meningiomas.

BACKGROUND: Numerous neoplasms within the CNS have been reported as radiogenic in origin; radiation-induced meningiomas are at least five times more numerous than gliomas or sarcomas in the world literature. METHODS: The authors review 10 cases of cerebral meningiomas following high-dose radiotherapy in patients operated for neoplasm of the nervous system. The pathologic and clinical aspects of this unusual complication are analyzed in all cases in the world literature. RESULTS: There is a female predominance (F-M ratio: 3:2) and the patients are young (mean age: 33.1 years; median: 29 years). The average latency period is 14.4 years (range: 9-21 years). The first disease is acute lymphocytic leukemia (ALL) in 40% of cases. Radiation induced meningiomas are atypical in four cases. Recurrence was observed in one case without malignant transformation. CONCLUSION: High-dose radiation-induced meningiomas have the following characteristics: (1) children appear particularly sensitive to the development of this tumor; (2) there is a female predominance, otherwise than is observed in low-dose meningioma; (3) these tumors present a peak frequency in the third decade of life; and (4) frequently, these tumors are atypical and recur. Finally, it is essential that every new case be reported to throw light on this particular pathologic correlation with its many grey areas.

Solitary cerebral metastasis from lung cancer with very long survival: report of two cases and review of the literature.

Solitary cerebral metastases from lung cancer are not uncommon clinical events. Whatever treatment is adopted, long-term survival is rare. Very rare indeed are reports of patients surviving the discovery of lung cancer and brain metastasis for 10 years or more. Indeed, only 16 cases have been reported to our knowledge. We report two further cases, stressing the importance of correct clinicopathological staging so that treatment may be conducted in the way most likely to ensure longer and better survival and, pending a therapeutic breakthrough, to increase the number of long-term survivors.